2. Academic Validation
  3. Ancistrobrevidines A-C and related naphthylisoquinoline alkaloids with cytotoxic activities against HeLa and pancreatic cancer cells, from the liana Ancistrocladus abbreviatus

Ancistrobrevidines A-C and related naphthylisoquinoline alkaloids with cytotoxic activities against HeLa and pancreatic cancer cells, from the liana Ancistrocladus abbreviatus

  • Bioorg Med Chem. 2021 Jan 15:30:115950. doi: 10.1016/j.bmc.2020.115950.
Shaimaa Fayez 1,  Alessia Cacciatore 2,  Sijia Sun 3,  Minjo Kim 3,  Laurent Aké Assi 4,  Doris Feineis 2,  Suresh Awale 5,  Gerhard Bringmann 6
Affiliations

Affiliations

  • 1 Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street 1, 11566 Cairo, Egypt.
  • 2 Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
  • 3 Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
  • 4 Centre National de Floristique, Conservatoire et Jardin Botaniques, Université d' Abidjan, Abidjan 08, Cote d'Ivoire.
  • 5 Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: suresh@inm.u-toyama.ac.jp.
  • 6 Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. Electronic address: bringman@chemie.uni-wuerzburg.de.
PMID: 33383442 DOI: 10.1016/j.bmc.2020.115950
Abstract

From the leaves of Ancistrocladus abbreviatus (Ancistrocladaceae), six 5,1'-coupled naphthyldihydroisoquinoline Alkaloids were isolated, ancistrobrevidines A-C (5-7), 5-epi-dioncophyllidine C2 (10), 6-O-methylhamatinine (8), and 6-O-methylancistectorine A3 (9); the two latter compounds were already known from related Plants. Most strikingly, this series comprises Alkaloids belonging to three different subclasses of naphthylisoquinolines. Ancistrobrevidine C (7) and the Alkaloids 8 and 9, displaying the S-configuration at C-3 and an oxygen function at C-6, are three further representatives of the large subgroup of 5,1'-coupled Ancistrocladaceae-type compounds found in nature. 5-epi-Dioncophyllidine C2 (10), lacking an oxygen function at C-6 and having the R-configuration at C-3, is only the third representative of a 5,1'-linked Dioncophyllaceae-type naphthylisoquinoline. Likewise rare are 5,1'-coupled hybrid-type Alkaloids, which are 6-oxygenated and 3R-configured. The ancistrobrevidines A (5) and B (6) are the only second and third examples of such 5,1'-linked naphthylisoquinolines in Ancistrocladus species showing the landmarks of both, Ancistrocladaceae- and Dioncophyllaceae-type naphthylisoquinolines. In the roots of A. abbreviatus, two further unprecedented 5,1'-coupled Alkaloids were discovered, ancistrobreviquinones A (11) and B (12), consisting of a 3,4-naphthoquinone portion coupled to a tetrahydroisoquinoline subunit. They are the very first quinoid naphthylisoquinolines possessing an ortho-diketone entity. Ancistrobrevidine C (7) exerted pronounced antiproliferative activities against HeLa cervical Cancer cells and preferential cytotoxicity towards PANC-1 human pancreatic Cancer cells under nutrient-deprived conditions following the antiausterity approach. Moreover, 7 suppressed the migration of PANC-1 cells and significantly inhibited colony formation under nutrient-rich conditions in a concentration-dependent manner, and induced dramatic alteration in cell morphology, leading to cell death.

Keywords

Ancistrobrevidines; Ancistrobreviquinones; Ancistrocladus abbreviatus; Anticancer agents; Naphthylisoquinoline alkaloids; Pancreatic cancer.

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